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PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides.

ABSTRACT: The cell wall of the human bacterial pathogen Group A Streptococcus (GAS) consists of peptidoglycan decorated with the Lancefield group A carbohydrate (GAC). GAC is a promising target for the development of GAS vaccines. In this study, employing chemical, compositional, and NMR methods, we show that GAC is attached to peptidoglycan via glucosamine 1-phosphate. This structural feature makes the GAC-peptidoglycan linkage highly sensitive to cleavage by nitrous acid and resistant to mild acid conditions. Using this characteristic of the GAS cell wall, we identify PplD as a protein required for deacetylation of linkage N-acetylglucosamine (GlcNAc). X-ray structural analysis indicates that PplD performs catalysis via a modified acid/base mechanism. Genetic surveys in silico together with functional analysis indicate that PplD homologs deacetylate the polysaccharide linkage in many streptococcal species. We further demonstrate that introduction of positive charges to the cell wall by GlcNAc deacetylation protects GAS against host cationic antimicrobial proteins.

SUBMITTER: Rush JS

PROVIDER: S-EPMC8807736 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides.

Rush Jeffrey S JS Parajuli Prakash P Ruda Alessandro A Li Jian J Pohane Amol Arunrao AA Zamakhaeva Svetlana S Rahman Mohammad M MM Chang Jennifer C JC Gogos Artemis A Kenner Cameron W CW Lambeau Gérard G Federle Michael J MJ Korotkov Konstantin V KV Widmalm Göran G Korotkova Natalia N

Nature communications 20220201 1

The cell wall of the human bacterial pathogen Group A Streptococcus (GAS) consists of peptidoglycan decorated with the Lancefield group A carbohydrate (GAC). GAC is a promising target for the development of GAS vaccines. In this study, employing chemical, compositional, and NMR methods, we show that GAC is attached to peptidoglycan via glucosamine 1-phosphate. This structural feature makes the GAC-peptidoglycan linkage highly sensitive to cleavage by nitrous acid and resistant to mild acid condi ...[more]

PMID: 35105886

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Dataset Information

PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides.

Publications

PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides.

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